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Treatment of Rheumatic Diseases with Pycnogenol

1. Potential mechanism of action, active constituents, and available preparations 

Pycnogenol is an extract derived from the bark of the maritime pine (Pinus pinaster), which is native to the Mediterranean region and is attributed antioxidant and anti-inflammatory properties. The MMI Pharmindex lists 18 products classified as non-prescription dietary supplements containing between 30 and 100 mg of Pycnogenol.

2. Overview of the scientific evidence for clinical efficacy in the literature

The present literature review (see Appendix 1) examined whether this plant-derived compound may exert potential therapeutic effects in inflammatory rheumatic diseases. [1] Despite a targeted search for studies on rheumatoid arthritis (RA), no relevant publication was identified; instead, only studies on Sjögren syndrome, systemic lupus erythematosus (SLE), lupus vasculitis, and Behçet syndrome were found [1] [2] [3] [4] [5].

The identified studies describe positive effects of Pycnogenol. Luzzi et al. reported a significant reduction in erythrocyte sedimentation rate and an improvement in clinical symptoms in Sjögren syndrome [4]. In an open-label registry study with a mixed cohort of patients with SLE, Behçet syndrome, Sjögren syndrome, and polyarteritis nodosa, Belcaro et al. found a significant reduction in interleukin-6 as well as decreased use of glucocorticoids and nonsteroidal anti-inflammatory drugs in the Pycnogenol group [1]. Further studies in patients with systemic lupus and vasculitis documented improvements in parameters such as photosensitivity, oral ulceration, significantly lower autoantibody titers against double-stranded DNA, and fewer cases of thrombocytopenia [2]. A critical limitation of the study by Cesarone et al. is that no classification criteria were used to define systemic lupus and vasculitis [2]. In addition, one study demonstrated a significant reduction in oxidative stress and disease activity in SLE [5].

Furthermore, studies with small sample sizes and short treatment duration found a significant reduction in pain in knee osteoarthritis [6] [7] [8]. These findings may also be extended to hand osteoarthritis [9]. At the same time, a reduction in the use of analgesic medication was observed [6] [7]. Improvements in grip strength in hand osteoarthritis and walking distance in knee osteoarthritis were also reported [9] [7].

3. Potential applications in rheumatology and expected beneficial effects

Based on these small studies with limited patient numbers, it may be discussed whether a beneficial effect on disease activity could exist in systemic lupus erythematosus, Behçet syndrome, and Sjögren syndrome. With regard to the treatment of osteoarthritis, Pycnogenol was associated with a reduction in osteoarthritis-related pain.

4. Potential adverse effects and limitations

It must be emphasized critically that the studies have significant methodological deficiencies. The investigations were open-label, uncontrolled, and based on small sample sizes, which substantially limits the strength of the conclusions. The endpoints used—mostly nonspecific inflammatory markers or subjective symptom scales—also do not permit a robust assessment of clinical relevance. [1]. No comparative studies with established disease-modifying drugs are available. Furthermore, adverse effects are not discussed.

5. Final recommendation of the commission

There are currently insufficient data to support the use of Pycnogenol for the treatment of inflammatory rheumatic diseases. Studies with clearly defined clinical endpoints would be required to enable a sound evaluation.

If patients with osteoarthritis explicitly request a phytotherapeutic supplement in addition to an established treatment concept, Pycnogenol may be mentioned as an option for self-medication. However, the weak level of evidence should be clearly communicated.

References

1. Belcaro G, Hu S, Cesarone MR, Scipione V, Scipione C, Dugall M, Cornelli U, Cox D, Hosoi M, Feragalli B et al: Supplementation with Pycnogenol® relieves symptoms of chronic inflammatory diseases with a significant vasculitis component: a pilot registry study. Minerva Med 2025, 116(2):106-112.

2. Cesarone MR, Belcaro G, Corsi M, Scipione C, Scipione V, Hu S, Hosoi M, Ledda A, Feragalli B, Cotellese R: Supplementary management with Pycnogenol® in patients with lupus vasculitis in remission phases: a pilot, concept registry study. Minerva Cardioangiol 2020, 68(2):146-152.

3. Hu S, Belcaro G, Ledda A, Corsi M, Cotellese R, Feragalli B, Hosoi M, Dugall M, Torino-Rodriguez P, Cesarone MR: Behçet syndrome: effects of Pycnogenol® supplementation during regression phases. Minerva Cardioangiol 2018, 66(4):386-390.

4. Luzzi R, Belcaro G, Hu S, Feragalli B, Hosoi M, Dugall M, Ledda A: Efficacy of Pycnogenol® supplementation in remission phases of Sjögren syndrome. Minerva Cardioangiol 2018, 66(5):543-546.

5. Stefanescu M, Matache C, Onu A, Tanaseanu S, Dragomir C, Constantinescu I, Schönlau F, Rohdewald P, Szegli G: Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients. Phytother Res 2001, 15(8):698-704.

6. Feragalli B, Dugall M, Luzzi R, Ledda A, Hosoi M, Belcaro G, Cesarone MR: Pycnogenol®: supplementary management of symptomatic osteoarthritis with a patch. An observational registry study. Minerva Endocrinol 2019, 44(1):97-101.

7. Belcaro G, Cesarone MR, Errichi S, Zulli C, Errichi BM, Vinciguerra G, Ledda A, Di Renzo A, Stuard S, Dugall M et al: Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects. Phytother Res 2008, 22(4):518-523.

8. Jessberger S, Högger P, Genest F, Salter DM, Seefried L: Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study. BMC Complement Altern Med 2017, 17(1):537.

9. Cesarone MR, Belcaro G, Cox D, Scipione V, Scipione C, Dugall M, Hosoi M, Feragalli B, Hu S, Coppazuccari F et al: Supplementary management of symptomatic hand osteoarthritis with Pycnogenol®. Minerva Surg 2024, 79(5):539-544.


Appendix 


Appendix 1: Assessment of the evidence base: design of the PubMed search.

KeywordsReferences identified in PubMed
pycnogenol rheumatic or pycnogenol arthritisn = 1
pycnogenol and vasculitis rheumaticn = 0
pycnogenol and vasculitis rheumatoidn = 0
pycnogenol and connective tissue diseasen = 3
pycnogenol and psoriatic arthritis n = 0
pycnogenol and spondyloarthritisn = 0
pycnogenol and systemic sclerosisn = 0
pycnogenol and sharp sydromen = 0
pycnogenol and sjögren syndromen = 2
pycnogenol and lupusn = 3
pycnogenol and giant cell arteriitisn = 0
pycnogenol and arteriitis temporalisn = 0
pycnogenol and panarteriitis nodosan = 1
pycnogenol and granulomatosis with polyangiitisn = 0
pycnogenol and osteoarthritisn = 4
pycnogenol and microscopic polyangiitisn = 0
pycnogenol and eosinophilic granulomatosis with polyangiitisn = 0
pycnogenol and Morbus Bechetn = 1
pinus pinaster rheumatic or pinus pinaster arthritisn = 0
pinus pinaster and vasculitis rheumatoidn = 0
pinus pinaster and connective tissue diseasen = 0
pinus pinaster and osteoarthritisn = 0

Duplicate studies were excluded from the analysis. [1] Animal studies and reviews were likewise excluded.


Appendix 2: Overview of the evaluated publications.

PublikationKollektivErgebnisse
Luzzi R et al. [4]
  • n = 30
  • standard treatment: n = 14
  • St standard treatment plus Pycnogenol n = 16
  • comparative study
  • Significant decrease in erythrocyte sedimentation rate
  • Significant improvement in the symptoms of Sjögren's syndrome 
  • Reduction in glucocorticoid use
Belcaro G et al. [1]
  • n = 124
  • Pycnogenol supplementation (150 mg/day): n = 63
  • Control group: n = 61
  • 4 weeks; open-label registry study
  • Assessment of improvements in inflammatory symptoms
  • Rating symptoms on a scale of 0 to 10
  • A significant decrease in erythrocyte sedimentation rate and interleukin-6 levels in the supplementation group compared to the control group
  • Significantly lower use of nonsteroidal anti-inflammatory drugs and glucocorticoids in the supplementation group
  • Significant reduction in inflammatory symptoms
Cesarone MR et al. [2]
  • n = 26
  • disease entity: systemic lupus and vasculitis 
  • Standard medication: n = 12
  • Pycnogenol group (150 mg/day): n = 14
  • Study duration: 8 weeks
  • Pycnogenol supplementation in patients with lupus vasculitis in remission
  • Very well tolerated
  • Lower incidence of photosensitivity, oral ulcers, hematuria, leukopenia, lymphopenia, thrombocytopenia, double-stranded DNA antibodies, and positive antiphospholipid antibodies in the Pycnogenol group
  • No significant difference in terms of skin involvement, serositis, anemia, neurological symptoms, and anti-Smith antibodies
  • A significantly greater reduction in oxidative stress in the Pycnogenol group
Stefanescu et al. [5]
  • n = 11
  • Standard medication n = 6
  • Pycnogenol group (Tag 0-30: 120 mg/day, subsequently day: 31-60: 60 mg/day) n = 5 
  • Treatment with Pycnogenol led to a reduction in reactive oxygen species, erythrocyte sedimentation rate, and compared to the placebo group
Hu et al. [3]
  • n = 44
  • Pycnogenol group (150 mg/day) 
  • Study duration: 4 weeks
  • note: no full-text access
  • Significant reduction in ulcers and pain caused by dryness
  • Decreased erythrocyte sedimentation rate and leukocytosis, as well as a positive response to the pathogy test
Cesarone et al. [9]
  • retrospective comparison group with standard medication (diclofenac): n = 20
  • Pycnogenol group (150 mg/day) plus standard medication 
  • Study duration: 4 weeks
  • note: no full-text access
  • Significant reduction in hand pain, pain medication use, and laboratory markers of inflammation (erythrocyte sedimentation rate and C-reactive protein), along with an increase in grip strength in the Pycnogenol group
Feragalli et al. [6]
  • observational registry study 
  • n = 67
  • Pycnogenol group (110 mg applied twice daily via a transdermal therapeutic system): n = 33
  • Control group: n = 34


 

  • Significant improvement in knee osteoarthritis symptoms and laboratory markers of inflammation (C-reactive protein and erythrocyte sedimentation rate), accompanied by a reduction in the use of nonsteroidal anti-inflammatory drugs
Jessberger et al. [8]
  • Pycnogenol group (100 mg twice a day): n = 15
  • Control group: n = 15
  • Study duration: 3 weeks
  • Significant downregulation of cartilage degradation markers (MMP3 and MMP13) and proinflammatory cytokines (interleukin 1β)
Belcaro et al. [7]
  • Studiendesign: Doppelblind, placebokontrollierte
  • Pycnogenol group (100 mg twice a day): n = 77
  • Control group: n = 79
  • Study duration: 3 months
  • Significant reduction in the WOMAC (Western Ontario and McMaster Universities) Index (Pycnogenol group 56% versus control group 9.6%)
  • Increase in walking distance (Pycnogenol group: 130 m vs. control group: 23 m)
  • Reduction in the use of pain medication (Pycnogenol group: 58% vs. 1%)
  • Decrease in gastrointestinal complications (Pycnogenol group: 63% vs. 3%)

 

Last updates: March 11, 2026

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